Secretion does not appear to have a physiological role in release of insulin following intravenous glucose and arginine administration. This has been shown by the fact that infusions of secretin which reach physiological levels do not directly stimulate or augment insulin output to glucose or arginine. Standardized meals evoke small but insignificant icreases in plasma secretin. Oral Alcohol does not stimulate endogenous secretin release. Physiological levels of secretin and octapeptide CCK attained by infusion do not increase insulin responses to intravenous glucose and arginine. However, gastric inhibitory peptide (GIP) released by corn oil ingestion, although having no effect on glucose and insulin levels per se, increases (2 fold the insulin responses to intravenous glucose (but not arginine) in normal and diabetic subjects. Thus, GIP appears to have the insulin augmenting properties originally ascribed to secretin. These data also indicate that diabetic subjects have an intact entero-insulin axis and their insulin secretory defect may be limited to glucose.